Parkinson’s disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly people. However, the etiology and pathogenesis of PD are still unclear and there is a lack of reliable biomarkers for early molecular diagnosis. Parkin (encoded by PARK2) is a ubiquitin E3 ligase that participates in mitochondrial homeostasis, the ubiquitin-proteasome pathway, oxidative stress response, and cell death pathways, which are involved in the pathogenesis of PD. However, Parkin is also expressed in peripheral blood lymphocytes (PBLs). In this study, permanent lymphocyte lines were established from the peripheral blood of sporadic PD (sPD) patients, PARK2 mutation carriers, and healthy controls. Reactive oxygen species (ROS), function of the mitochondrial respiratory chain complex I, and apoptosis were analyzed in the PBLs. There was no significant difference in ROS, mitochondrial respiratory chain complex I, and apoptosis between the experimental groups and the control group without paraquat treatment. Compared with the control group of healthy subjects, we found an increase of ROS (control , sPD , and C441R ) and apoptosis, as well as a decline in the function of mitochondrial respiratory chain complex I in PBLs of PARK2 mutation carriers and sPD after the treatment of paraquat (control , sPD , and C441R ). Moreover, overexpression of the wild-type (WT) PARK2 in HeLa cells and immortalized PBLs could rescue mitochondrial function and partially inhibit apoptosis following paraquat treatment, while the C441R mutation could not. Thus, ROS levels, activity of mitochondrial respiratory chain complex I, and apoptosis of PBLs are potential diagnostic biomarkers of PD.

中文翻译：

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与帕金森氏病相关的PARK2突变增强了外周血淋巴细胞对百草枯的脆弱性

帕金森氏病（PD）是中老年人中第二常见的神经退行性疾病。然而，PD的病因和发病机制仍不清楚，并且缺乏用于早期分子诊断的可靠生物标志物。Parkin（由PARK2编码）是一种泛素E3连接酶，参与线粒体的体内稳态，泛素-蛋白酶体途径，氧化应激反应和细胞死亡途径，这些都与PD的发病机理有关。但是，帕金也在外周血淋巴细胞（PBL）中表达。在这项研究中，从散发性PD（sPD）患者PARK2的外周血中建立了永久性淋巴细胞系突变携带者和健康对照。在PBL中分析了活性氧（ROS），线粒体呼吸链复合体I的功能以及细胞凋亡。在未经百草枯治疗的实验组和对照组之间，ROS，线粒体呼吸链复合物I和凋亡均无显着差异。与健康受试者的对照组相比，我们发现ROS（对照组， sPD，和C441R）和凋亡，以及在PBL中在线粒体呼吸链复合物I的功能下降PARK2百草枯的处理（控制之后突变携带者和SPD， sPD，和C441R）。此外，百草枯处理后，野生型（WT） PARK2在HeLa细胞和永生化PBL中的过表达可以挽救线粒体功能并部分抑制细胞凋亡，而C441R突变则不能。因此，ROS水平，线粒体呼吸链复合体I的活性和PBL的凋亡是PD的潜在诊断生物标志物。